Figure 4

Model of signaling pathways for LTP and central plasticity caused by injuries. A. In the ACC, activity triggers release excitatory neurotransmitter glutamate (Glu: filled circles). Activation of glutamate NMDA receptors leads to an increase in postsynaptic Ca²⁺ in dendritic spines. Ca²⁺ serves as an important intracellular signal for triggering a series of biochemical events that contribute to the expression of LTP. Neural Ca²⁺ binds to CaM and leads to activation of calcium-stimulated ACs, including AC1 and AC8 and Ca²⁺/CaM dependent protein kinases (PKC, CaMKII and CaMKIV). The Ca/CaM dependent protein kinases phorsphoryalte glutamate AMPA receptors, increasing their sensitivity to glutamate. B. In the ACC synapses, the possible postsynaptic trafficking of AMPA GluR1 receptors contributes to synaptic potentiation. C. Inflammatory or nerve injuries cause both presynaptic and postsynaptic changes in the ACC synapses. Enhanced release of glutamate as well as postsynaptic changes in AMPA receptor mediated responses contribute to enhanced noxious sensory information with in the brain, a possible cellular mechanism for persistent pain.